Oral mucosa shows a marked regional variation in structure and such variation appears to be related to regional differences in function. A similar pattern of variation is seen in the skin. Epithelia are continuously regenerating structures. There is some evidence to suggest that a continuous influence of the subepithelial connective tissue is required to maintain regional specificity of structure. Many of the adverse pathological processes occurring in the oral cavity, ranging from periodontal disease to carcinoma are associated with, or are causally related to, changes in the maintenance of epithelial structure and information which leads to an understanding of this process would be of great value. As working hypotheses, we propose a) that epithelial maintenace can be considered in relation to the control of three types of cellular activity; rates of synthesis, types of synthesis and establishment of tissue architecture and b) that a basic pattern of epithelial cell differentiation is continuously modulated by the subepithelial connective tissue into a site specific pattern of organization. The objectives of the proposed research are to evaluate whether: a) all epithelia have the same basic pattern of differentiation, b) there is a regional specificity of the connective tissue, c) all epithelia are capable of remodulation, d) the organization, rate and type of epithelial synthesis are independently controlled and e) there is a specific cell type responsible for the role of maintaining epithelial integrity and specificity. We propose to investigae this problem using separation techniques which we have recently developed to examine a selected, diverse range of oral epithelial and epidermal specimens following both homotypic and heterotypic transplantation of epithelium and connective tissue into protected sites in histocompatible mice and to evaluate the results by examining the effects of such tissue interchanges on morphological structure, rates of cell production and patterns of synthesis of different types of keratin and cell surface materials.